Safe and effective sofosbuvir-based therapy in patients with mental health disease on hepatitis C virus treatment

Safe and effective sofosbuvir-based therapy in patients with mental health disease on hepatitis C virus treatment
Lydia Shuk Yee Tang, Jack Masur, Zayani Sims, Amy Nelson, Anu Osinusi, Anita Kohli, Sarah Kattakuzhy, Michael Polis, Shyam Kottilil

World J Hepatol. Nov 8, 2016; 8(31): 1318-1326
Published online Nov 8, 2016. doi: 10.4254/WJH.v8.i31.1318

Abstract

AIM

To study impact of baseline mental health disease on hepatitis C virus (HCV) treatment; and Beck’s Depression Inventory (BDI) changes with sofosbuvir- and interferon-based therapy.

METHODS

This is a retrospective cohort study of participants from 5 studies enrolled from single center trials conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, MD, United States. All participants were adults with chronic HCV genotype 1 infection and naïve to HCV therapy. Two of the studies included HCV mono-infected participants only (SPARE, SYNERGY-A), and 3 included human immunodeficiency virus (HIV)/HCV co-infected participants only (ERADICATE, PFINPK, and ALBIN). Patients were treated for HCV with 3 different regimens: Sofosbuvir and ribavirin in the SPARE trial, ledipasvir and sofosbuvir in SYNERGY-A and ERADICATE trials, and pegylated interferon (IFN) and ribavirin for 48 wk in the PIFNPK and ALBIN trials. Participants with baseline mental health disease (MHD) were identified (defined as either a DSM IV diagnosis of major depression, bipolar disorder, schizophrenia, generalized anxiety, and post-traumatic stress disorder or requiring anti-depressants, antipsychotics, mood stabilizers or psychotropics prescribed by a psychiatrist). For our first aim, we compared sustained virologic response (SVR) and adherence (pill counts, study visits, and in 25 patients, blood levels of the sofosbuvir metabolite, GS-331007) within each study. For our second aim, only patients with HIV coinfection were evaluated. BDI scores were obtained pre-treatment, during treatment, and post-treatment among participants treated with sofosbuvir-based therapy, and compared to scores from participants treated with interferon-based therapy. Statistical differences for both aims were analyzed by Fisher’s Exact, and t-test with significance defined as a P value less than 0.05.

RESULTS

Baseline characteristics did not differ significantly between all participants with and without MHD groups treated with sofosbuvir-based therapy. Among patients treated with sofosbuvir-based therapy, the percentage of patients with MHD who achieved SVR was the same as those without (SPARE: 60.9% of those MHD compared to 67.6% in those without, P = 0.78; SYNERGY-A: 100% of both groups; ERADICATE: 100% compared to 97.1%). There was no statistically significant difference in pill counts, adherence to study visits between groups, nor mean serum concentrations of GS-331007 for each group at week 2 of treatment (P = 0.72). Among patients with HIV co-infection, pre-treatment BDI scores were similar among patients treated with sofosbuvir, and those treated with interferon (sofosbuvir-based 5.24, IFN-based 6.96; P = 0.14); however, a dichotomous effect on was observed during treatment. Among participants treated with directly acting antiviral (DAA)-based therapy, mean BDI scores decreased from 5.24 (pre-treatment) to 3.28 during treatment (1.96 decrease, P = 0.0034) and 2.82 post-treatment. The decrease in mean score from pre- to post-treatment was statistically significant (-2.42, P = 0.0012). Among participants treated with IFN-based therapy, mean BDI score increased from 6.96 at pre-treatment to 9.19 during treatment (an increase of 2.46 points, P = 0.1), and then decreased back to baseline post-treatment (mean BDI score 6.3, P = 0.54). Overall change in mean BDI scores from pre-treatment to during treatment among participants treated with DAA-based and IFN-therapy was statistically significant (-1.96 and +2.23, respectively; P = 0.0032). This change remained statistically significant when analysis was restricted to participants who achieved SVR (-2.0 and +4.36, respectively; P = 0.0004).

CONCLUSION

Sofosbuvir-based therapy is safe and well tolerated in patients with MHD. A decline in BDI associated with sofosbuvir-based HCV treatment suggests additional MHD benefits, although the duration of these effects is unknown.

Core tip: The prevalence of mental health disease (MHD) among patients with chronic hepatitis C virus (HCV) can be high. However, patients with MHD may be marginalized with respect to HCV therapy and MHD is one of the most frequently cited reason for exclusion from HCV therapy. HCV therapy has evolved from interferon-based to directly acting antiviral (DAA)-based therapy with excellent tolerability and efficacy. Our study found that baseline MHD did not impact efficacy nor treatment adherence to sofosbuvir-based therapy. Furthermore, we found that Becks Depression Inventory scores improved with sofosbuvir-based therapy, suggesting that HCV treatment with the newer DAA therapies may have additional mental health benefits.

DISCUSSION ONLY

View Full Text Article - World J Hepatol. Nov 8, 2016; 8(31): 1318-1326
Published online Nov 8, 2016. doi: 10.4254/WJH.v8.i31.1318

Sofosbuvir-based therapy was equally effective among participants with MHD, and among those without MHD. Patients with baseline MHD demonstrated similar levels of adherence with study visits, study drugs, and achieved similar rates of SVR to those who did not have a baseline MHD diagnosis. Furthermore, among participants with HIV/HCV coinfection treated with DAA therapy, we observed a statistically significant improvement in BDI scores during and after the end of treatment time point (post-treatment) compared to baseline (pre-treatment), while participants treated with IFN-based therapy saw no significant change in BDI scores.

In a study of 4084 United States veterans, psychiatric disease was identified as a predictor of non-treatment (odds ratio = 9.45)[29]. Furthermore, due to shared transmission routes, HIV/HCV coinfection can be high among certain cohorts. A cross sectional study of a large cohort of patients with HIV found that 21% were coinfected with HCV. Among these patients with HIV/HCV coinfection, depression severity scores were higher, and antidepressant medications were more often prescribed, compared to patients with HIV mono-infection[30]. Concern for emergent or worsening of neuropsychiatric side effects associated with interferon-based HCV therapy resulted in treatment deferment even for patients with stable MHD[14,31,32]. The treatment of chronic HCV, however, has evolved to interferon-free, all-oral, DAA regimens. Concerns regarding adherence to and subsequent success with DAA regimens among patients with MHD remains to be addressed.

This study has 2 aims: Firstly, to address the impact of baseline MHD on adherence to and subsequent success with DAA regimens among patients with MHD; and secondly, to describe the change in BDI scores among patients treated with a sofosbuvir-based regimen (ledipasvir-sofosbuvir) and compare this to the change among patients treated with IFN-based therapy.

In the current study, we combined results from three studies using interferon-free regimens. We compared the effect of MHD on outcome (SVR) and three modalities of adherence (pill count, study visits and serum levels of GS-331007). The prevalence of MHD among the 3 studies (approximately 35%) was comparable to the baseline prevalence reported in other studies[7,10-14]. This study demonstrates that patients with MHD can achieve SVR at rates comparable to those without MHD. Six patients from SPARE did not complete treatment, 5 of which were identified as suffering from MHD but only one discontinuation from study could be attributed to MHD as determined by evaluation by the principal investigator. This suggests that these interferon-free regimens did not affect adherence and subsequent efficacy of therapy.

For our second aim, we analyzed baseline pre-treatment, during treatment, and post-treatment BDI scores among HIV/HCV coinfected participants treated with a sofosbuvir-based regimen (ledipasvir-sofosbuvir) in the ERADICATE study and coinfected participants treated with IFN-based therapy (PFINPK and ALBIN). Mean changes from baseline to during and to post-treatment were compared within, and between, each treatment group. We demonstrate that despite similar baseline BDI scores in both treatment groups, participants treated with ledipasvir-sofosbuvir saw a decrease in BDI scores during treatment and post-treatment compared to baseline. However, participants treated with IFN-based therapy did not see any change in BDI scores. In fact, when treatment groups were compared to each other and adjusted for participants who achieved SVR, the overall decrease in BDI score from baseline to post-treatment among participants treated with ledipasvir-sofosbuvir was significantly different compared to the overall increase in BDI score among participants treated with IFN-based therapy. It is conceivable that successful treatment of HCV alone should be associated with improvement in mental health. However, our findings suggest that sofosbuvir-based (and possibly any IFN-free) anti-HCV therapy may have additional mental health benefits beyond end of treatment.

This study is strengthened by multiple measures of adherence: Pill counts for all 3 studies; and in SPARE study visits with the additional objective measure of serum levels of the sofosbuvir metabolite GS-331007 at week 2 of therapy. Adherence to oral DAA therapy was high in all 3 studies, regardless of baseline MHD status, with no significant differences in pill counts, study visits, and serum GS-331007 levels between those with and without MHD. Whether the high adherence was a consequence of participant selection and the more intensive adherence interventions and counseling that are inherent to clinical trials, or related to the improved tolerability and ease of administration of the medications cannot be determined.

Limitations of this study include its small sample sizes for the three patient groups analyzed and therefore may not be sufficiently powered to detect differences. This did not allow for addressing the hypothesis that a regimen of fewer pills for shorter duration (1 pill once a day in ERADICATE and SYNERGY-A for 12 wk compared to several pills a day for 24 wk in SPARE) was associated with significantly higher adherence. Furthermore, combining more than one study did result in a non-homogenous study population, most evident in the difference in baseline fibrosis stage among the participants undergoing BDI evaluation. Finally, this study did not include patients with severe, uncontrolled MHD therefore may have been biased towards those who already had a background of good adherence or lower BDI scores.

We hope that these preliminary findings will open the dialogue to further expand eligibility to those with MHD and lead to further, larger studies involving patients with more challenging characteristics: Not just those with baseline MHD, but also those with substance abuse - two diagnoses which are frequently paired[5-8]. Inclusion of these marginalized groups will be necessary if we are to gain an advantage in the battle to eradicate hepatitis C.

In conclusion, our study supports that patients with baseline MHD can be successfully engaged and treated with DAA therapies, and that sofosbuvir-based therapy is associated with improvement in BDI scores.

Continue to full text article - World J Hepatol. Nov 8, 2016; 8(31): 1318-1326

Alcohol use disorder and its impact on chronic hepatitis C virus and human immunodeficiency virus infections

Alcohol use disorder and its impact on chronic hepatitis C virus and human immunodeficiency virus infections
World J Hepatol. Nov 8, 2016; 8(31): 1295-1308
Published online Nov 8, 2016. doi: 10.4254/WJH.v8.i31.1295
Daniel Fuster, Arantza Sanvisens, Ferran Bolao, Inmaculada Rivas, Jordi Tor, Robert Muga    

Abstract
Alcohol use disorder (AUD) and hepatitis C virus (HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to interactions between AUD and HCV on immune responses, cytotoxicity, and oxidative stress. Although AUD and HCV infection are associated with increased morbidity and mortality, HCV antiviral therapy is less commonly prescribed in individuals with both conditions. AUD is also common in human immunodeficiency virus (HIV) infection, which negatively impacts proper HIV care and adherence to antiretroviral therapy, and liver disease. In addition, AUD and HCV infection are also frequent within a proportion of patients with HIV infection, which negatively impacts liver disease. This review summarizes the current knowledge regarding pathological interactions of AUD with hepatitis C infection, HIV infection, and HCV/HIV co-infection, as well as relating to AUD treatment interventions in these individuals.

Key Words: Hepatitis C virus, Human immunodeficiency virus, Hepatitis C virus/human immunodeficiency virus co-infection, Liver, Alcohol

Core tip: The present review is focused on alcohol use disorder and hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection, as well as HCV/HIV co-infection.
Citation: Fuster D, Sanvisens A, Bolao F, Rivas I, Tor J, Muga R. Alcohol use disorder and its impact on chronic hepatitis C virus and human immunodeficiency virus infections.

INTRODUCTION
Alcohol abuse is a major cause of preventable liver disease worldwide, and alcohol use disorder (AUD) is associated with substantial disease burden in western countries[1]. According to 5th edition of the Diagnostic and Statistical Manual of Mental Disorders[2], AUD encompasses both alcohol abuse and alcohol dependence. Table 1 presents the diagnostic criteria for AUD and other definitions of unhealthy alcohol use, such as the recommendations of the United States National Institute on Alcohol Abuse and Alcoholism.

In the United States, almost 9% of the adult population meets the AUD criteria and alcohol contributes to 79000 deaths annually[3]. Within the European Union, alcohol misuse causes 14% of deaths in men and nearly 8% of deaths in women, with alcohol-related mortality disproportionally impacting young people[4]. In Spain, unhealthy alcohol use is exhibited by 5% of the population between 15 and 64 years old, and 15% report at least one binge drinking episode within the prior year[5]. Moreover, the pattern of binge drinking is becoming increasingly prevalent, mainly among young individuals.

Per capita alcohol consumption is strongly correlated with liver cirrhosis mortality rates globally[6]. However, the short- and long-term impacts of binge drinking with regards to the development and severity of alcoholic liver disease (ALD) are not yet known. Per capita alcohol consumption is strongly correlated with liver cirrhosis mortality rates across countries[5]. Notably, the medical literature reveals wide heterogeneity in the methods used to assess alcohol exposure, and it can be challenging to analyze time-varying exposures like alcohol consumption over time[7].

Epidemiology of AUD in hepatitis C virus and human immunodeficiency virus infection
Addressing alcohol use is critical in the management of hepatitis C virus (HCV)-infected patients, as AUD is associated with poor clinical outcomes and liver-related deaths in this patient group[8]. Compared to the general population, HCV-infected adults tend to consume greater amounts of ethanol[9], being over twice as likely to consume more than one alcoholic drink per day (34% vs 14%) and almost 8 times more likely to consume over three drinks per day (19% vs 2%)[10].

Moreover, alcohol abuse is associated with concomitant use of illegal substances, and 30% to 50% of patients with a history of substance abuse consume alcohol[11]. This is highly important since 2/3 of new HCV infections in the western world are associated with drug injection[12]. Accordingly, the prevalence of HCV infection is higher among patients with AUD who are current or past injecting drug users[13]. Within a cohort of patients with AUD admitted for hospital detoxification in the Barcelona area, HCV prevalence was as high as 20%[14]. However, other researchers in Spain reported a much lower prevalence of 3.5%[13], possibly due to differences in patient selection.

The prevalence of HCV infection is confounded by the degree of liver disease. Cross-sectional studies performed in hepatology clinics showed that HCV prevalence was higher among patients with advanced liver fibrosis, and almost universal among HCV-infected patients with hepatocellular carcinoma[15,16]. On the other hand, HCV prevalence ranged from 1% to 10% in community-oriented studies of individuals with AUD but without clinically apparent liver disease[17,18]. A recent meta-analysis including 24 studies reported that the average weighted prevalence of HCV infection among patients with AUD was 16.3%[13].

AUD may also be common among human immunodeficiency virus (HIV)/AIDS patients, with a prevalence ranging from 30% to 50%[19]. High prevalences of alcohol consumption have been reported in HIV/AIDS cohort studies from the United States[20,21], Europe[22-24], South Africa[25], and other parts of the world[26]. In the Women’s Interagency HIV Study, 14%-24% of female HIV/AIDS participants reported hazardous alcohol use within the past year[27]. On the other hand, patients with AUD show a lower prevalence of HIV infection than HCV infection[14], which is confounded by prevalence of injection drug use.

AUD AND CHRONIC HCV INFECTION
Effect of alcohol on HCV replication
Alcohol metabolites apparently enhance viral protein expression as well as the heterogeneity of HCV quasispecies[28]. Some authors describe RNA-HCV increases among patients who use alcohol[29]. However, a meta-analysis performed by Anand et al[30] in 2005 showed no association between RNA-HCV and alcohol consumption.

Impact of alcohol on HCV infection persistence
Spontaneous resolution of HCV infection requires an early and wide immune response against HCV viral proteins[31]. Once acute HCV infection is controlled, the presence of memory T-cell populations is associated with reduced persistence of infection in re-exposed individuals[32]. HCV infection persistence is also associated with loss of specific T-cell proliferation, and reduced migration of effector T cells to the liver[33]. HCV-infected patients with AUD show functional impairment of dendritic cells[34], which partly explains the association between alcohol use and lower odds of spontaneous HCV resolution[35,36].

Effect of alcohol on HCV-related immunity
Mice that are chronically exposed to ethanol exhibit diminished immune responses to HCV-core protein, mainly due to impaired maturation of dendritic cells[34]. In HCV-infected patients, dendritic cells present impaired allostimulation capacity, which is more apparent in the presence of alcohol[34]. Alcohol and HCV infection exert synergistic effects, suppressing major histocompatibility complex class II[37] via functional impairment of the proteasome (intracellular protein complexes that degrade unnecessary or damaged proteins) and alterations in interferon signaling[38]. This could partly explain the lower efficacy of interferon-based HCV treatment regimens among patients with AUD[39].

Effect of alcohol on cytotoxicity
Enhanced hepatocyte apoptosis is observed in HCV infection, which is apparently associated with impaired immune responses rather than directly attributable to the viral infection[40]. Hepatocyte apoptosis is mediated by cytotoxic T cells and natural killer cells via caspase activity[40]. BCL-2 protein is associated with mitochondrial permeability, and its expression is reduced in HCV-infected hepatocytes[41]. Alcohol seems to enhance hepatocyte apoptosis through down-regulation of BCL-2 expression[40].

Alcohol and oxidative stress
The HCV core viral protein is associated with higher oxidative stress. It binds the mitochondrial wall, facilitating calcium entrance, electron transport, and increased reactive oxygen species, which results in increased oxidative stress that damages the cell[42]. This protein also targets microsomal triglyceride transfer protein activity, thus modifying hepatic very-low-density lipoprotein particle assembly and secretion, which leads to liver steatosis[43]. Moreover, the HCV core viral protein alters the oxidant/antioxidant state of the liver in the absence of inflammation, consequently producing mitochondrial DNA damage[44].

In HCV-core transgenic mice, chronic ethanol administration is associated with higher lipid peroxidation and synergic induction of TGF-β1 and hepatic stellate cells[45]. The HCV-core protein cooperates with ethanol to activate some p38 mitogen-activated protein kinase pathways, resulting in polygene modulation, and contributing to liver disease pathogenesis[46]. In alcohol-fed NS5A transgenic mice, the synergistic effect between HCV infection and alcohol is dependent on mechanisms involving Toll-like receptor 4, which belongs to the innate immune system[47]. Alcohol consumption and HCV infection impact FOXO3 expression, thus impairing antioxidant capacity in the liver[48].

In humans, indirect evidence suggests that oxidative stress is associated with more extensive liver injury in patients with AUD and HCV infection, as they tend to show higher serum levels of malondialdehyde (a lipid peroxidation product), poor glutathione peroxidase activity, and stimulation of Th1 response cytokines[49]. Moreover, patients with AUD present major lipid peroxidation, and the loss of antioxidant capacity is associated with liver fibrosis[50]. Among HCV-infected patients who drink alcohol, liver fibrosis is independently associated with liver steatosis, oxidative stress, age, and iron deposits in the liver[51].

Alcohol and progression of HCV-related liver disease
Alcohol consumption is associated with more extensive progression of HCV-related liver damage[52,53]. No safe level of alcohol consumption has been described, as even HCV-infected patients who drink moderate amounts of alcohol (30 g/d) experience progressive liver fibrosis[54-56]. A meta-analysis assessed 20 studies that were published between 1995 and 2004, and found that the relative risk of progression to liver cirrhosis or decompensated liver disease among HCV-infected patients was 2.3 times higher, with a 95%CI of 1.7-3.3, among those who drank alcohol compared to abstainers[52]. However, the majority of included studies were performed in liver units, and thus might be biased towards patients with more severe forms of liver disease[52]. Alcohol consumption is also associated with higher risks of cirrhosis decompensation and liver-related death[57]. Moreover, alcohol consumption has a synergistic effect with chronic hepatitis C, increasing the risk of liver cancer[58].

Assessment of liver disease in patients with AUD and HCV infection
In both HCV infection and ALD, liver fibrosis is the main prognostic factor of liver disease progression[59,60]. Although liver biopsy is the gold standard for liver fibrosis assessment[61], it is associated with several rare complications and is not usually performed in patients with substance use disorders[62]. Recent reports describe the estimation of liver fibrosis using several non-invasive biological markers derived from laboratory parameters routinely used in clinical practice, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count.

Of these potential markers, FIB-4[63] and the aspartate aminotransferase/platelet ratio index (APRI)[64] have been validated against the gold standard of liver biopsy in HCV-monoinfected patients as well as HCV/HIV-coinfected patients[65-68]. These markers perform better for detecting either the absence of liver fibrosis or the presence of advanced liver fibrosis[63,64]. However, clinical experience using these markers in patients with AUD is limited[69], and concerns have been raised about the possibility of overestimating liver fibrosis in patients with alcoholic steatohepatitis. Moreover, ALD is a formal contraindication for the use of Pohl’s score[70]-an index that uses aminotransferase levels and platelet count. Transient elastography has also been used to assess liver fibrosis in ALD[71], but the presence of severe liver steatosis may distort results, leading to overestimation of advanced liver fibrosis[72].

In prior studies, we have defined alcohol-related liver disease (ARLD) as the presence of any two of the following criteria: Elevated AST to between 74 and 300 U/L, AST/ALT ≥ 2, and total bilirubin > 1.2 mg/dL[73,74]. Within a cohort of AUD patients admitted for hospital detoxification in metropolitan Barcelona, Spain, 14.6% met those criteria, and ARLD was associated with mid-term mortality[75].

Impact of HCV infection on hospitalizations and mortality of patients with AUD
As previously mentioned, alcohol use is associated with worse prognosis in HCV-related liver disease. It is estimated that 36% of liver cirrhosis among HCV-infected individuals is attributable to alcohol use[76]. HCV infection also has a deleterious impact on clinical outcomes among patients with AUD[77-80]. Tsui et al[77] identified 6354 AUD-related hospital admissions, and reported that the HCV-positive patients were twice as likely to die (4.4% vs 2.4%, P < 0.01), and showed significantly longer hospital stays (19% longer, 95%CI: 12%-27%). Another study included patients from the United States Nationwide Inpatient Sample Dataset who had a primary or a secondary discharge diagnosis of alcoholic hepatitis, and reported that HCV-positive patients had higher mortality with an odds ratio (OR) of 1.29 (95%CI: 1.12-1.49, P < 0.01)[78].

Patients with AUD who are exposed to HCV infection probably differ from those who are not exposed with regards to co-morbidities or behaviors associated with poorer survival, such as the use of illicit drugs[81]. However, even in studies that have accounted for various lifestyle factors, HCV infection remains associated with both overall mortality, showing a hazard ratio (HR) of 2.55 (95%CI: 1.50-4.33, P < 0.01), and liver-related mortality (HR = 3.24, 95%CI: 1.18-8.94, P = 0.02)[79].

In our study of 675 AUD patients admitted for hospital detoxification, we examined the impact of HCV infection on mortality. Our results showed that HCV infection was associated with higher mortality, and that this effect was more apparent in patients with younger ages at admission (HR = 3.1, 95%CI: 1.3-7.3, P < 0.01) and those who were co-infected with HCV/HIV (HR = 3.9, 95%CI: 2.1-7.1, P < 0.01)[80]. In the same Barcelona cohort, we recently reported that AUD patients with HCV mono-infection showed an increased risk of liver-related death in comparison to AUD patients without HCV-infection (HR = 3.92, 95%CI: 2.03-7.59)[82].

Interferon-based treatment of HCV infection in patients with AUD
In the era of HCV antiviral therapy including interferon, infection treatment was challenging in individuals who consumed alcohol[8]. In fact, alcohol use was a major reason for a lack of HCV treatment[83,84]. Several researchers analyzed strategies to extend HCV treatment to patients with unhealthy alcohol use. Le Lan et al[85] performed an observational study of HCV treatment in alcohol-drinking patients, in which drinking in moderation was encouraged but not required. Of the study population, 30% continuously abstained, 34% consumed low-risk amounts of alcohol, and 36% continued to drink risky amounts. The overall sustained viral response (SVR) rate was 48% with no difference observed between abstainers and low-risk drinkers[85], confirming prior results in a Swiss HCV cohort[86].

Evon et al[87] performed a randomized clinical trial in the United States, which included 9-mo intervention comprising counseling, case management, and motivational interviewing for patients ineligible for HCV treatment (31% due to alcohol abuse). The intervention was associated with a 2.38 relative risk of being deemed eligible (95%CI: 1.21-4.68). The groups did not differ with regards to the proportion of patients that eventually received HCV antiviral therapy[87].

Interferon-free treatment of HCV infection in patients with AUD
The advent of direct-acting antivirals and interferon-free regimens has dramatically changed the landscape of HCV treatment, with most registration trials and pilot real-life experiences reporting SVR rates of over 90%[88]. Although treatment is now more feasible for patients with substance use disorders[89,90], to date, very few patients with AUD have been included in clinical trials[91-93].

The current American Association for the Study of Liver Diseases - Infectious Diseases of America guidelines for HCV treatment advocate abstinence from alcohol[94]. When appropriate, these guidelines suggest interventions to facilitate the cessation of alcohol consumption, ranging from brief interventions for patients with low alcohol intake[94], to referral to mutual help groups and specialty treatment for patients with established AUD[94]. While alcohol consumption is not a formal contraindication for HCV treatment, a year of abstinence from alcohol is thought to be necessary to achieve adequate treatment adherence[95].

There remains a need for a change in the provision of HCV treatment such that patients with AUD and HCV infection can benefit from viral eradication. Expansion of the capacity of primary care clinics or addiction clinics to provide HCV treatment has been successfully tested in several areas of the United States[96] and Australia[90]. These experiences should be replicated worldwide to more effectively treat difficult-to-reach populations[97].

AUD treatment in patients with HCV infection
Brief interventions involving feedback and discussion of the negative consequences of alcohol abuse are efficacious at motivating reduced alcohol consumption among among patients with unhealthy alcohol use[98], but not patients with alcohol dependence. Such brief interventions can be targeted towards patients with HCV infection, with delivery at the primary care level or in hepatology clinics[94,99]. More intensive treatments, such as motivational enhancement therapy, can also reduce the number of drinking days among patients with chronic HCV infection[100]. Other type of interventions, such as group therapy, can reportedly motivate abstinence from alcohol in 44% of patients in an HCV clinic[101].

Table 2 summarizes the various treatment strategies for patients with AUD. Specialty treatment should be favored in such cases, and patients should be offered detoxification; specific pharmacotherapy including disulfiram, acamprosate, naltrexone, or nalmefene; and psychosocial support[3]. Some researchers have reported satisfactory results with baclofene in patients with overt end-stage liver disease[102].

AUD AND HIV INFECTION
Effect of alcohol on the immune system
The combined effects of alcohol and HIV on the immune system have been investigated in simian models[103]. Alcohol and HIV infection show a synergistic impact on gastrointestinal tract integrity, causing initial depletion of intestinal CD4 cells[104,105]. Loss of intestinal wall integrity is associated with increased permeability, microbial translocation, and immune activation[106]. Immune activation is crucial for HIV disease progression[107], and is reportedly a better predictor of disease progression than HIV viral load[106,108]. While alcohol seems to impact the adaptive immune responses to HIV infection in animal models, the results in humans are mixed[103]. In a study of HIV-infected patients, blood alcohol levels relative to alcohol intake were higher before antiretroviral treatment compared to after treatment[109].

Alcohol and HIV disease progression
Prior to widespread use of antiretroviral therapy (ART), epidemiological data suggested that alcohol use was not associated with HIV disease progression[110,111]. However, following the advent of ART, several authors have reported reduced ART effectiveness among patients with AUD[19,112]. In 2003, Samet et al[113] investigated a cohort of HIV-infected patients, and reported cross-sectional data suggesting that alcohol consumption negatively impacted HIV disease progression. Alcohol consumption was associated with lower CD4 cell counts and higher HIV viral loads in patients receiving ART. A later longitudinal study of the same cohort demonstrated that heavy alcohol use in patients not receiving ART was associated with lower CD4 cell counts but not with HIV viral load[114].

Chander et al[115] at John Hopkins University reported that heavy alcohol consumption was associated with reduced viral suppression of HIV infection and lower treatment adherence. Wu et al[116] investigated 325 subjects receiving ART and found that, after adjusting for adherence, daily drinkers showed a nearly four-fold increase in the odds of detectable HIV viral load. This association was non-significant for regular drinkers. Their results further showed that alcohol use was not associated with CD4 cell count, and that alcohol consumption was not associated with HIV viral load among patients not receiving ART[116]. On the other hand, Baum et al[117] investigated HIV-infected patients receiving ART, and reported that alcohol use was associated with lower CD4 cell counts, greater risk of showing a CD4 cell count of < 200, and an increased HIV viral load over time.

More recent studies indicate that the benefits of ART seem to outweigh the detrimental effects of alcohol use, reinforcing the importance of initiating ART and ensuring adequate treatment adherence[118]. A study in a Swiss HIV cohort revealed no effect of alcohol consumption on either virological failure or CD4 cell count, both among ART-receiving and ART-naïve patients[119]. That study also demonstrated that heavy drinkers were more likely to interrupt ART; however, only 2.8% of participants were heavy drinkers[119]. A recent French study of HIV/AIDS patients reported that low levels of alcohol consumption (< 10 g/d) were associated with higher CD4 counts compared to in abstainers[120]. However, the beneficial effects of such low levels of alcohol consumption may be confounded by other healthier behaviors exhibited by moderate drinkers[121].

Overall, evidence acquired during the first decade of ART use suggested that AUD may impact HIV disease progression; however, more recent studies do not support those findings. These contradictory results may be partly explained by poor adherence to treatment and barriers to proper medical care associated with AUD.

Alcohol and comorbidities
Alcohol use is associated with unprotected sex and syringe sharing, thus elevating the risks of HIV acquisition and transmission[122-124]. Moreover, alcohol use is associated with higher prevalence of depressive symptoms[125], which can influence ART initiation[126], treatment adherence[127], treatment discontinuation[128], and disease progression[129,130]. Other substance use disorders frequently co-exist in patients who exhibit alcohol abuse[11], which is also associated with poorer treatment adherence, reduced HIV viral suppression, and lower retention in care[112,131].

Heavy alcohol use is related to liver disease among patients with HIV infection[132,133], and is also associated with cardiovascular disease[134] and exacerbations of chronic obstructive pulmonary disease[135]. A systematic review of 13 studies reported that heavy alcohol use was associated with elevated risk of cardiovascular disease, with a risk ratio of 1.78 (95%CI: 1.09-2.93)[134].

Alcohol and mortality in HIV infection
Alcohol is commonly regarded as an underappreciated modifiable risk factor in individuals with HIV infection, with or without HCV co-infection[116]. A retrospective study from northern California evaluated data from between 1996 and 2005, and found that higher mortality rates were associated with diagnosis of a substance use disorder (alcohol only, drug only, or alcohol and drug)[136]. In the HIV-LIVE cohort of HIV-positive patients with alcohol problems, short-term mortality was associated with homelessness and drug use[137], and long-term mortality was associated with HCV infection and high levels of inflammation markers[79,138]. A study from the VACS cohort revealed that even non-hazardous levels of alcohol consumption were associated with decreased survival[139]. Recent data from the same VACS cohort shows that among HIV-positive participants, alcohol use was associated with greater physiological injury. Moreover, within this cohort, a greater risk of mortality was associated with an Alcohol Use Disorders Identification Test value of ≥ 4 drinks/mo (HR = 1.25, 95%CI: 1.09-1.44), and of ≥ 30 drinks/mo (HR = 1.30, 95%CI: 1.14-1.50)[140].

HIV treatment in patients with AUD
Alcohol use co-existing with other substance use is associated with lower quality of HIV care[141] and poor retention in care[131]. A systematic review of 53 studies published between 2010 and 2015 showed that 77% of studies revealed that alcohol use was negatively associated with the HIV treatment cascade, i.e., access to care, ART prescription, and treatment adherence[142]. This suggests that unhealthy alcohol use should be targeted to increase the proportion of HIV/AIDS patients who achieve viral suppression.

Even modest alcohol consumption has been associated with poor ART adherence[139]. Hendershot et al[143] performed a meta-analysis of 40 studies, and showed that patients who drank relatively more were 50%-60% less likely to adhere to ART compared with those who abstained or drank relatively less. Alcohol consumption appears to be dose-dependently related to ART adherence[115], and shows a temporal relationship to missed ART treatments[144].
AUD treatment in HIV-infected patients

Among HIV/AIDS patients who drink alcohol, brief interventions are reportedly efficacious for reducing the frequency of alcohol use and the frequency of unprotected sex[145,146]. However, patients abusing alcohol might need more intensive treatment. Some authors report that the addition of motivational interviewing[147] and problem solving therapy may be necessary to improve ART adherence[148]. An intervention called retention through enhanced personal contact has also been tested to improve retention among HIV-positive patients with alcohol use or mental illness[149].

Chander et al[150] recently performed a cross-sectional survey among HIV care providers, and found that although the majority reported that they usually screen for alcohol use, only 10% used a formal screening tool. Moreover, knowledge of pharmacotherapy for AUD was low, and most care providers referred patients to outside resources for treatment[150].

AUD AND HCV/HIV CO-INFECTION

A proportion of patients with both AUD and HCV infection also have HIV infection. In fact, HCV/HIV co-infection is clinically relevant among individuals with history of injection drug use[151]. HIV infection is associated with faster progression of HCV-related liver fibrosis[152,153] as well as earlier occurrence of decompensated liver disease[154,155], liver cancer[156], and liver-related death[157]. During the interferon era, co-infection with HIV compromised HCV treatment response[158,159]. However, interferon-free regimens have greatly increased the efficacy of HCV antiviral treatment among co-infected patients, both in clinical trials[160] and in real-life scenarios[161,162]. On the other hand, HCV infection is associated with increased risk of ART-related liver toxicity[163], which is even higher with concurrent alcohol use[164]. In cases of HCV/HIV co-infection, alcohol use is also associated with poorer treatment adherence[165], and seems to increase HCV RNA levels[166,167].

Until recently, the impact of alcohol use on HCV-related liver disease in HIV-infected patients had not received much attention in the literature. Older studies suggest that alcohol use is associated with biopsy-proven liver fibrosis in cases of co-infection[152,168]. However, studies using non-invasive methods have produced mixed results, highlighting the shortcomings of non-invasive methods-including methods relying on ALT, AST, and platelets-in patients with ALD[70,69]. Table 3 summarizes the different studies that have used non-invasive methods to evaluate liver fibrosis in patients with AUD and HCV infection or HCV/HIV co-infection.

A cross-sectional study in an urban HIV/AIDS cohort revealed that heavy alcohol use was associated with advanced liver fibrosis measured using the APRI score[169]. However, when the patients were stratified by HCV infection, high APRI score was associated with hazardous alcohol use only among patients without HCV infection[169]. Blackard et al[170] investigated a cohort of women, and demonstrated that alcohol use was not associated with FIB-4 values among HCV/HIV co-infected patients. Within our cohort of AUD patients, FIB-4 was significantly higher among HCV/HIV co-infected patients compared to in HCV monoinfected patients[171]. In the HIV-LIVE cohort, lifetime alcohol consumption[172] was not associated with the absence of liver fibrosis (FIB-4 < 1.45), and similar results were found for the presence of advanced liver fibrosis (FIB-4 ≥ 3.25) and among patients with HCV infection[173]. A study in the VACS cohort-which included a larger number of patients and a different measure of alcohol consumption-reported greater risks of advanced liver fibrosis (measured based on FIB-4) among co-infected patients who exhibited nonhazardous drinking (OR = 14.2, 95%CI: 5.91-34.0) or hazardous/binge drinking (OR = 18.9, 95%CI: 7.98-44.8), or who had alcohol-related diagnoses (OR = 25.2, 95%CI: 10.6-59.7) relative to uninfected individuals who were nonhazardous drinkers[174]. The somewhat discordant results among studies may be partly due to differences in the methods used to describe alcohol use and other characteristics of the study population[169-174].

French researchers investigating HCV/HIV co-infected patients recently found that advanced liver fibrosis (measured with transient elastography) was more common among those with an alcohol-related diagnosis (OR = 3.06, 95%CI: 1.42-6.60) compared to non-hazardous drinkers[175]. Elastography may be more reliable than laboratory markers for assessing liver fibrosis in HCV/HIV co-infected patients with AUD. Additionally, the combination of HCV infection and alcohol use is associated with greater mortality within HIV/AIDS cohorts[79,176], highlighting the need to further address alcohol use in co-infection. Although it can be challenging, it is feasible to reduce alcohol use in the setting of HCV/HIV co-infection[177].

CONCLUSION

To reduce the impact of HCV, HIV and ethanol on liver disease, patients with AUD should be screened for HCV and HIV infection, and interventions should focus on both reducing alcohol consumption and treating viral infections. Moreover, patients with HCV infection or HCV/HIV co-infection should be screened for unhealthy alcohol use to prevent end-stage liver disease. Several treatment interventions are efficacious for reducing alcohol consumption among individuals with HCV infection or HCV/HIV co-infection.

In settings where AUD often coexists with other substance use and viral co-infections, higher levels of co-morbidities are expected. Health care facilities for treatment interventions and multidisciplinary approaches must be widely accessible for managing AUD and associated diseases.

References

Source - Full Text - World J Hepatol. Nov 8, 2016; 8(31): 1295-1308
Published online Nov 8, 2016. doi: 10.4254/WJH.v8.i31.1295

The Cost Of A Cure: Revisiting Medicare Part D And Hepatitis C Drugs

The Cost Of A Cure: Revisiting Medicare Part D And Hepatitis C Drugs
Two years ago, soon after the Food & Drug Administration (FDA) approved the first breakthrough treatment for hepatitis C, we wrote about the potential cost of a cure to Medicare Part D and its beneficiaries. For that piece, we used the best available data to estimate the number of people on Medicare who might seek treatment and the impact on Medicare spending. Here we revisit our earlier analysis using new data released by CMS, and consider both the ongoing impact of hepatitis C drugs for Part D and the broader implications for Medicare of new high-priced drugs entering the market.​

Continue reading....

How the liver dances to a day/night rhythm

How the liver dances to a day/night rhythm Ecole Polytechnique Fédérale de Lausanne

Credit: Daniel Mauvoisin/EPFL

This is a diagram showing the different expression of proteins in liver cells during the day/night cycle.

Following the day-night cycle, the liver has its own metabolic rhythm. Using cutting-edge proteomics, scientists at EPFL and the Nestlé Institute of Health Sciences have now identified over 500 liver proteins that change in abundance over the course of the day in the cell nucleus, opening a new dimension of metabolism.

Biological processes occurring in our bodies are far from static, but instead the rhythm of most of them is dictated by an internal, 24-hour biological metronome called the 'circadian clock'. During each day-night cycle, many physiological processes follow oscillatory waves orchestrated by this clock, allowing them to adapt and anticipate the body's demands at a given time of day. EPFL scientists have now used cutting-edge proteomics to monitor the temporal accumulation of over 5,000 different proteins in the nucleus of mouse liver cells, and have identified over 500 that are connected to the 24-hours cycle. The study, published in Cell Metabolism is the first in this field in terms of scale and resolution, and has significant implications regarding our understanding of the interconnections between rhythmic metabolism and nutrition.

Biology is affected by time

Our bodies follow the day-night, or "diurnal", cycle, by finely tuning metabolic processes to time of day -- this is why we can sleep for hours without going hungry through the night but can barely stand eight hours after breakfast, or why jet lag can sometimes cause digestive problems. Such oscillations are the focus of "chronobiology" a research field that looks at how biological functions are organized in time and how disease could arise when this time organization is disturbed.

This regulation of metabolism is connected to how our genes produce proteins. Many genes follow our circadian clock by adjusting the rate at which they produce proteins, and knowing which genes do this would help us understand how metabolism changes over the course of a day. Unfortunately, even though the human genome was mapped out more than a decade ago, investigating how genes control the production of proteins on a time-dependent scale is still difficult, mostly because of the sheer number of proteins present in a cell.

500 liver proteins affected by the day-night cycle

Felix Naef at EPFL and Frédéric Gachon at the the Nestlé Institute of Health Sciences, have now made a breakthrough in our understanding of time-dependent metabolism. Working only the nuclei of liver cells, the scientists identified 5000 proteins of which more than 500 were affected during the diurnal cycle; more specifically, the proteins entered and left the nucleus over the course of the day. In addition, they found that key cellular functions such as DNA repair, ribosome biogenesis, cell cycle and chromosome regulation (polyploidy) were also affected by diurnal regulation.

To counteract the huge complexity of the proteome, the researchers only focused on the cell's nucleus instead of the entire cell. The nucleus is where genes produce proteins that are then sent to various locations around the cell. As such, the nucleus is very sensitive to environmental and biochemical signals, and can translate these into molecular responses by controlling protein production.

The scientists used biochemical techniques to isolate the nuclei from liver cells taken from mice with and without a functioning circadian clock. Having isolated the nuclei, they extracted all the proteins from them and analyzed them with mass spectrometry.

Cutting-edge proteomics

Like genomics for genes, proteomics is the field of digital biology where computers are used to create detailed databases and maps of the complete set of an organism's proteins. The scientists used a technique called SILAC coupled with high-resolution proteomics, which can efficiently quantify proteins -- in this case, the proteins are quantified in the nucleus at different time-points throughout a 24-hour cycle. By doing this, they were able to get a global picture of how the diurnal cycle affects protein accumulation in the liver nucleus. "

While many studies approach physiological functions statically, our temporal approach gave us unprecedented insights into how metabolism cycles over a day," says Felix Naef. "We were surprised by how pervasively nuclear functions in liver are influenced by the day and night and feeding cycles."

"The study also shows that this quantitative proteomics approach is an excellent tool for systematic analysis of cell functions," says Frédéric Gachon. "This would not be feasible with conventional proteomic techniques."

This work involves a collaboration between EPFL's Institute of Bioengineering and the Nestlé Institute of Health Sciences, with contributions from the University of Lausanne, and the Institut de Génétique Moléculaire de Montpellier. It was funded by the Swiss National Science Foundation, EPFL, the European Research Council (ERC), and the Leenaards Foundation.

Reference

Jingkui Wang, Daniel Mauvoisin, Eva Martin, Florian Atger, Antonio Núñes Galindo, Loïc Dayon, Federico Sizzano, Alessio Palini, Martin Kussmann, Patrice Waridel, Manfredo Quadroni, Vjekoslav Duli?, Felix Naef, and Frédéric Gachon. Nuclear proteomics uncovers diurnal regulatory landscapes in mouse liver. Cell Metabolism 03 November 2016. DOI: 10.1016/j.cmet.2016.10.003

Gilead's Q3 Bombshell: No More Hepatitis C R&D

Gilead's Q3 Bombshell: No More Hepatitis C R&D
Todd Campbell

Nov 2, 2016 at 4:41PM                    

Gilead Sciences (NASDAQ: GILD) is a Goliath in hepatitis C treatment; however, the company is shifting its research spending in the future away from hepatitis C to other indications, and that decision could have big implications on the hepatitis C market in the long term...  

Gilead Sciences' news could give AbbVie and Merck & Co. an opportunity to gain share if they continue developing new therapies that can compete better. AbbVie's ABT-493 plus ABT-530 mash-up, for example, is in late-stage studies that include an eight-week dosing option. If trials are successful, that therapy could compete more effectively against the short-duration Harvoni regimen in genotype 1...

Continue reading....

2016 November HCV Newsletters and Headlines

November HCV Newsletters and Headlines

Hope everyone had a great Halloween, our family sure did! Did the kids count all that candy yet? No? Did you sneak a few favorites? Yes? Consider reading this over at Al D. Rodriguez Liver Foundation; Halloween Goodies: Threat or Treat?

Excerpt;

Candies and other sweet goodies are now commonly made with artificial sweeteners, which are more of a threat than a treat to our bodies’ health.  

How do sugar substitutes — particularly the alternative processed fructose — damage the liver? 

First, one of the problems with artificial sweeteners is that they are marketed as either healthier or safer alternatives because — as some “experts” say — “they pass through your body undigested.” In response to this train of thought, people are consuming fructose in greater, massive quantities. Yet the may be unaware that fructose, when excessively consumed, turns into a chronic, dose-dependent liver toxin.

After putting back some of that candy you swiped, check out this months index of newsletters, related articles and interesting blog updates. Enjoy!

In The News
Gilead's Q3 Bombshell: No More Hepatitis C R&D
Gilead Sciences (NASDAQ: GILD) is a Goliath in hepatitis C treatment; however, the company is shifting its research spending in the future away from hepatitis C to other indications, and that decision could have big implications on the hepatitis C market in the long term. Let's take a closer look at the hepatitis C market and Gilead Sciences' decision to press the pause button on hepatitis C R&D.

Distress and depression with type 2 diabetes tied to skipping meds
(Reuters Health) - People with type 2 diabetes who also have symptoms of distress or depression are more likely than others to miss or skip their diabetes medications, according to a recent study.

High-protein diets reduce liver fat
According to a new nutritional study conducted by the German Institute of Human Nutrition (DIfE) on individuals with type 2 diabetes, high-protein diets reduced liver fat by up to 48 percent within six weeks. It did not matter whether the diet was mainly based on plant or animal protein. ​

Acute hepatitis after heavy energy drink use 'a warning to the consumer,' liver specialist says
A construction worker who consumed an excessive amount of energy drinks developed a rare case of acute hepatitis, say doctors who want patients to know about the potential risks to the liver from such over-consumption.

Herbal and dietary supplements are known to be potentially toxic to the liver, but the association is commonly overlooked, Dr. Jennifer Nicole Harb of the University of Florida College of Medicine and her co-authors said in Tuesday's online issue of BMJ Case Reports.
Read the article, here...

Gilead sales of Hepatitis C drugs slump
Gilead Sciences Inc. on Tuesday said sales of hepatitis C drugs Harvoni and Sovaldi missed expectations and slumped in the third-quarter, as the biopharmaceutical company faces challenges from rival drugs and pricing pressures.

Newsletters

HCV Advocate
The HCV Advocate newsletter is a valuable resource designed to provide the hepatitis C community with monthly updates on events, clinical research, and education.

November Newsletter
HCV Advocate's November newsletter is out with a must read article about discussing treatment with your doctor. The article hit on all the important questions and answers, for example; What can you do if your doctor won’t prescribe hepatitis C treatment, or wants to prescribe an older regimen, when clearly there are newer ones available? Another wonderful HealthWise article written by Lucinda K. Porter, RN.

HCV Advocate is patient friendly, so easy to read, especially when breaking down clinical information. Alan Franciscus writes about two clinical trials; the first one is about positive health outcomes of curing people infected with chronic hepatitis C - followed by a study of low rates of relapse after being cured of chronic hepatitis C. In addition the newsletter has a drug pipeline update as well.  Finally a new Easy C fact sheet on the importance of testing for hepatitis B before initiating HCV direct-acting antiviral therapy.

Read the November newsletter, here.... and all newsletters, here... 
HCV Advocate Website, here... HCV Advocate Clinical Trials Reference Guide, here.... and HCV Medications Blog, here...
____________________________________________

GI & Hepatology News
Over 17,000 gastroenterologists and hepatologists rely on GI & Hepatology News every month to cover the world of medicine with breaking news, on-site medical meeting coverage, and expert perspectives both in print and online. The official newspaper of the AGA Institute was launched in partnership with IMNG in January 2007.

November issue of GI & Hepatology News
Simple Interventions Markedly Improve Hepatitis Care
Fulminant HBV Reactivation Associated with HCV Drugs
NAFLD Estimated to Cost $103 Billion/Year
Download, here....
Past Issues
____________________________________________

The Hepatitis C Coalition

The Hepatitis C Coalition is a group of leading clinicians, patient organisations, professional groups, industry and other interested parties committed to the reduction of morbidity and mortality associated with hepatitis C and its eventual elimination. The Hepatitis C Coalition has funding from AbbVie, Gilead Sciences and Merck Sharp & Dohme.

Welcome to the October 2016 edition of the Hepatitis C Coalition's quarterly newsletter. This quarterly newsletter provides a concise summary of developments in hepatitis C for policymakers, clinicians, commissioners, local government, charities and others with an interest in hepatitis C or public health. News: including the relaunch of a national partnership group to produce a locally-led framework, the publication of Public Health England's annual report on hepatitis C in the UK, the Hepatitis C Trust judicial review and NHS England’s increased treatment rate of 12,500 for 2017/18 and the update to the Commissioning for Quality and Innovation (CQUIN) scheme.

Begin, here..... 

Past Newsletters

____________________________________________

The New York City Hepatitis C Task Force

The New York City Hepatitis C Task Force is a city-wide network of service providers and advocates concerned with hepatitis C and related issues. The groups come together to learn, share information and resources, network, and identify hepatitis C related needs in the community. Committees form to work on projects in order to meet needs identified by the community.

Hep Free NYC Newsletter
New Data on Hep B and Hep C in NYC, Hep C Ad Campaign in Brooklyn, BOOM!Health Feature and learn more about viral hepatitis and liver cancer.

Read the newsletter, here.... news updates, here....

____________________________________________

Treatment Action Group
Treatment Action Group (TAG) is a US-based HIV/AIDS activist organization formed in 1991 involved with worldwide efforts to increase research on treatments for HIV and for deadly co-infections that affect people with HIV, such as hepatitis C and tuberculosis.

TAGline Fall Issue
Treatment Action Group (TAG) published their TAGline fall issue with 8 must read articles including; Rallying the Multitude to Free the (generic) HCV Cure, ending the war on drugs, and access to safe and effective drugs. In case you missed it check out their fact sheet on the newly approved drug Epclusa, both in English and Spanish published in September.

Download Fall Issue here...,  Epclusa Fact Sheet, here..., All Current Publications, here....

____________________________________________

HCV Action

HCV Action brings together hepatitis C health professionals from across the patient pathway with the pharmaceutical industry and patient representatives to share expertise and good practice.

HCV Action e-update: October 2016

____________________________________________

NVHR Newsletter

The National Viral Hepatitis Roundtable is a broad coalition working to fight, and ultimately end, the hepatitis B and hepatitis C epidemics. We seek an aggressive response from policymakers, public health officials, medical and health care providers, the media, and the general public through our advocacy, education, and technical assistance.

Read about NVHR's new Policy Director, upcoming AASLD meeting, and more!

Begin, here....
____________________________________________

The American Liver Foundation
Liver Lowdown is the monthly general interest e-newsletter of the American Liver Foundation.

In case you missed it ALF recently published their special; Liver Awareness Month 2016 Issue.

October is big for the liver community. It's Liver Awareness Month- and it's also Liver Cancer Awareness Month, so we've teamed with Bayer to help raise awareness about the risk factors for this deadly disease. Learn more about liver cancer here.

American Liver Foundation, Great Lakes Division
November 2016 Newsletter  

Published on Nov 1, 2016  

Brought to You by the American Liver Foundation, Great Lakes Division

____________________________________________

Blog Updates

Hepatitis B Foundation
The Hepatitis B Foundation is a national nonprofit organization dedicated to finding a cure and improving the quality of life for those affected by hepatitis B worldwide. Our commitment includes funding focused research, promoting disease awareness, supporting immunization and treatment initiatives, and serving as the primary source of information for patients and their families, the medical and scientific community, and the general public.

Hepatitis B Foundation Expert Timothy Block Predicts Cure in the Next Three to Five Years
Today, the cofounder and president of the Hepatitis B Foundation, the Baruch S. Blumberg Institute and the Pennsylvania Biotechnology Center, is optimistic and predicts a cure will be developed in the three to five years.

View additional articles;
November 2016
October 2016
____________________________________________

HEP

Hep is an award-winning print and online brand for people living with and affected by viral hepatitis. Offering unparalleled editorial excellence since 2010, Hep and Hep Magazine are the go-to source for educational and social support for people living with hepatitis.

Worldwide, approximately 13 percent of patients with chronic hepatitis C infection have genotype 4.

By Lucinda K. Porter, RN

Treatment for Hepatitis C Genotype 4: No Longer Scary

Medicaid Insurance ACLU lawsuit Harvoni Unethical Discrimination

By Carleen McGuffey

Cures Available! Must meet Moral Minimum and Be Yellow.

Medications, vitamins, and supplements you take pass through your liver. Your liver is responsible for processing all of these substances.

By Connie M. Welch

Taking Care of Your Liver with Hep C

Read all blog updates, here....
____________________________________________

AGA Journals BLOG

Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology. She has worked as an editor at biomedical research journals and as a science writer for 15 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.

Updates

Can Direct-acting Antivirals Treatment of HCV Reactivate Herpesvirus Infection?
Researchers report reactivation of herpesvirus in 10 patients with hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents in the November issue of Clincial Gastroenterology and Hepatology. Christie Perelló et al performed a case series analysis of reactivation of herpesvirus in patients with HCV infection treated with DAA

Read more
____________________________________________

New Online
Recent Articles

HEPATITISC.NET
At HepatitisC.net we empower patients and caregivers to take control of Hepatitis C by providing a platform to learn, educate, and connect with peers and healthcare professionals.

How does gender/gender identity relate to HCV?

By Jenelle Marie Davis - November 1, 2016
People Born Male and Living as Male The main form of transmission for hepatitis C is IV drug use. Males are statistically more likely to begin to self-medicate and to use higher...

Moment In Time

By Daryl Luster - October 31, 2016
We are familiar with the phrase “one day at a time”. The meaning for me is to not worry about tomorrow so much and focus on getting through this day, whatever challenge...

Hepatitis C and Youth

By Daryl Luster - October 29, 2016
There are different age groups who have hep c. Youth is one group that in not spoken about as much as baby boomers or others who may have been exposed decades ago....

Read other recent HepatitisC.net headlines
Connect with others, join the forum
____________________________________________

Recommended Reading

Liver Cancer 

Risk of hepatitis B reactivation

Side Effects - HCV current DAA therapies

Welcome to Weekend Reading, today we offer a short review of recent warnings issued for hepatitis C direct-acting antivirals.

Available evidence suggests that HCV treatment with the new direct-acting antivirals (DAAs) should not be limited to patients with advanced liver disease.

Evidence shows value of treating all stages of chronic HCV

Evidence from 38 studies, involving 73,861 patients, showed a significant mortality benefit of achieving SVR in patients with all stages of fibrosis. Long-term studies with follow-ups of five to 12 years suggested that, particularly among non-cirrhotic patients, there was a significant decrease in mortality in SVR versus non-SVR groups.

Treatment for HCV across all genotypes

​The Changing HCV Landscape: Update on Treatment

DAAs for HCV infection have all but replaced IFN as the foundation of treatment for HCV across all genotypes. Among the major advantages of these oral regimens, beyond their remarkable efficacy, has been their relatively clean safety profile.

Testing prior to treatment, during, and after HCV therapy

Review: Clinical Laboratory Testing in the Era of Directly Acting Antiviral Therapies for Hepatitis C

Directly acting antiviral (DAA) combination therapies for chronic hepatitis C virus (HCV) infection are highly effective, but treatment decisions remain complex. Laboratory testing is important to evaluate a range of viral, host, and pharmacological factors when considering HCV treatment, and patients must be monitored during and after therapy for safety and to assess the viral response. In this review, we discuss the laboratory tests relevant for the treatment of HCV infection in the era of DAA therapy, grouped according to viral and host factors.

Side effects and medical contraindications

Emerging complexities with HCV DAA regimens: Less is still way more. 

The arrival of interferon-free direct acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) infection have been transformative. Treatment approaches which were once marred by frequent and potentially severe side effects, lack of patient and provider acceptance and marginal efficacy have been replaced by DAA regimens which can cure the vast majority of patients in 12 weeks with minimal to no side effects. Despite these tremendous advances in HCV therapy providers must recognize, as with any medication, that severe side effects and medical contraindications still exist for certain populations when using current DAA therapies.

Buyers’ Clubs: Generic versions of HCV drugs resulted in very high cure rates​

Generic hepatitis C

Keith Alcorn

Use of generic versions of direct-acting antivirals resulted in very high cure rates for people who obtained the products through three buyers’ clubs, indicating that the generics products are effective, according to three presentations at the International Congress on Drug Therapy in HIV Infection in Glasgow this week.

Recurrent viremia infrequent in hepatitis C

The prevalence of recurrent viremia was low among patients with hepatitis C who achieved sustained virologic response, data from a recently published study demonstrate.

Gilead to submit regulatory applications for SOF/VEL/VOX in the United States in the fourth quarter of 2016 and shortly thereafter in Europe.

Gilead SVR12 Rates SOF/VEL/VOX(GS-9857) Treatment-Naïve/Treatment-Experienced HCV Geno 1-6

Gilead Announces SVR12 Rates From Four Phase 3 Studies of a Once-Daily, Fixed-Dose Combination of Sofosbuvir, Velpatasvir and Voxilaprevir in Treatment-Naïve and Treatment-Experienced Genotype 1-6 Chronic HCV-Infected Patients

Full Text Article

​Sofosbuvir-Containing Regimens for Chronic Hepatitis C Are Successful in the Safety-Net Population: A Real-World Experience

Full Text Article

Safety, Tolerability, and Efficacy of Sofosbuvir Plus Ribavirin in Elderly Patients Infected with Hepatitis C Virus Genotype 2

____________________________________________

Off The Cuff

November/December ACP Internist
Washington Perspective

Health policy after the election
By Robert B. Doherty
The 2016 elections on Nov. 8 will have huge consequences for health policy.

If President Clinton is elected, she would largely pursue a continuity agenda: continuing to expand coverage options under the Affordable Care Act (ACA), including offering a “public option” to compete with private plans on the marketplaces, and offering people ages 55 to 65 the option to buy into Medicare coverage. She also will propose changes to stabilize the health insurance marketplaces in each state for small group and individual insurance to address the challenges of rising premiums and insurers pulling out of some of the markets, such as increasing the premium and cost-sharing subsidies and reinvigorating an expired re-insurance program to help insurers who enroll a less healthy mix of patients. However, the proportion of her agenda that could be enacted will depend on whether Democrats take control of the Senate from the GOP, whether the House remains under Republican control, and by what margins in both cases.
    
If President Trump is elected, his agenda is less clear, although he has pledged to work with Congress to repeal the ACA. He could replace it by allowing the selling of insurance across state lines, making health insurance premiums in the individual market fully tax-deductible, eliminating requirements that people buy insurance, and striking mandates on the benefits that plans must offer. However, how far he could go in repealing the ACA depends on which party controls the Senate and the House. Even if the GOP were to control both chambers, it would have to gain a filibuster-proof majority in the Senate. As a practical matter, it would be politically challenging to enact legislation that would take coverage away from the 20 million people currently covered under the ACA.
Read more...

Disclaimer in very small print; I did eat four peanut butter cups, and a bag of chips.

Until next time...
Tina

Evidence shows value of treating all stages of chronic HCV

Evidence shows value of treating all stages of chronic HCV

First Online: 25 October 2016

View Full Text Article;

Value of Treating All Stages of Chronic Hepatitis C: A Comprehensive Review of Clinical and Economic Evidence 

Article Summary

Available evidence suggests that HCV treatment with the new direct-acting antivirals (DAAs) should not be limited to patients with advanced liver disease.

A new literature review has provided an overview of the clinical and economic benefits of achieving SVR and to better understand the full value of chronic HCV treatment in all stages of liver disease. Overall, the review identified 354 studies involving more than 500,000 chronic HCV patients worldwide.

Evidence from 38 studies, involving 73,861 patients, showed a significant mortality benefit of achieving SVR in patients with all stages of fibrosis. Long-term studies with follow-ups of five to 12 years suggested that, particularly among non-cirrhotic patients, there was a significant decrease in mortality in SVR versus non-SVR groups.

Ninety-nine studies conducted in 235,891 chronic HCV patients in all stages of fibrosis showed that SVR reduced liver-related mortality, the incidence of hepatocellular carcinoma, and decompensation.

A total of 233 studies showed that chronic HCV infection was associated with several serious extrahepatic manifestations, some of which can have high mortality. Evidence from four modeling studies showed that delaying treatment to chronic HCV patient populations could significantly increase mortality, morbidity, and medical costs.

The review concludes that there is a robust body of evidence demonstrating diverse sources of value from achieving SVR in all stages of liver disease. While access to treatment is generally limited to late-stage patients, less restrictive treatment strategies that target HCV eradication have the potential to abate the burdens of mortality, liver morbidity and extrahepatic manifestations, and the associated healthcare costs.

Summary Source - https://www.basl.org.uk/

Reference

Value of treating all stages of chronic hepatitis C: a comprehensive review of clinical and economic evidence.

Nuño Solinís R, Arratibel Ugarte P, Rojo A et al. Infect Dis Ther. 2016 Oct 25. [Epub ahead of print]

The Complexities of Hepatocellular Carcinoma

The Complexities of Hepatocellular Carcinoma

Insights From: Richard S. Finn, MD, Geffen School of Medicine; Arndt Vogel, MD, Hannover Medical School

Published Online: Monday, Oct 31, 2016

Hepatocellular carcinoma, or liver cancer, is a very complex disease. Unlike a lot of malignancies that we treat, it almost always, 90% of the time, occurs in the presence of underlying liver disease, some degree of cirrhosis. The most common causes being hepatitis C, hepatitis B, alcohol use, and now, increasingly, the metabolic syndrome and nonalcoholic steatohepatitis. Because of these two diseases, there’s a competing risk for outcomes, both outcomes from liver disease and outcomes from a malignancy. And, therefore, its approach really requires, what we term, a “multidisciplinary team. “
Continue reading transcript, here.....